title: Can peripheral blood mononuclear cells be used as a proxy for mitochondrial dysfunction in vital organs during hemorrhagic shock and resuscitation?
abstract: BACKGROUND
  Although mitochondrial dysfunction is thought to contribute to the development of posttraumatic organ failure, current techniques to assess mitochondrial function in tissues are invasive and clinically impractical. We hypothesized that mitochondrial function in peripheral blood mononuclear cells (PBMCs) would reflect cellular respiration in other organs during hemorrhagic shock and resuscitation.
  
  
  METHODS
  Using a fixed-pressure HS model, Long-Evans rats were bled to a mean arterial pressure of 40 mmHg. When blood pressure could no longer be sustained without intermittent fluid infusion (decompensated HS), lactated Ringer's solution was incrementally infused to maintain the mean arterial pressure at 40 mmHg until 40% of the shed blood volume was returned (severe HS). Animals were then resuscitated with 4× total shed volume in lactated Ringer's solution over 60 min (resuscitation). Control animals underwent the same surgical procedures, but were not hemorrhaged. Animals were randomized to control (n = 6), decompensated HS (n = 6), severe HS (n = 6), or resuscitation (n = 6) groups. Kidney, liver, and heart tissues as well as PBMCs were harvested from animals in each group to measure mitochondrial oxygen consumption using high-resolution respirometry. Flow cytometry was used to assess mitochondrial membrane potential (Ψm) in PBMCs. One-way analysis of variance and Pearson correlations were performed.
  
  
  RESULTS
  Mitochondrial oxygen consumption decreased in all tissues, including PBMCs, following decompensated HS, severe HS, and resuscitation. However, the degree of impairment varied significantly across tissues during hemorrhagic shock and resuscitation. Of the tissues investigated, PBMC mitochondrial oxygen consumption and Ψm provided the closest correlation to kidney mitochondrial function during HS (complex I: r = 0.65; complex II: r = 0.65; complex IV: r = 0.52; P < 0.05). This association, however, disappeared with resuscitation. A weaker association between PBMC and heart mitochondrial function was observed, but no association was noted between PBMC and liver mitochondrial function.
  
  
  CONCLUSIONS
  All tissues including PBMCs demonstrated significant mitochondrial dysfunction following hemorrhagic shock and resuscitation. Although PBMC and kidney mitochondrial function correlated well during hemorrhagic shock, the variability in mitochondrial response across tissues over the spectrum of hemorrhagic shock and resuscitation limits the usefulness of using PBMCs as a proxy for tissue-specific cellular respiration.
authors.affiliation: *Department of Emergency Medicine, Gazi University School of Medicine, Ankara, Turkey; and †Children's Hospital of Philadelphia, Anesthesiology, Critical Care and Pediatrics, Perelman School of Medicine, ‡Division of Traumatology, Critical Care and Acute Care Surgery, §Perelman School of Medicine, and ∥Center for Resuscitation Science, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Mehmet Akif
authors.initials: MA
authors.lastname: Karamercan
authors.forename: Scott L
authors.initials: SL
authors.lastname: Weiss
authors.forename: Jose Paul Perales
authors.initials: JP
authors.lastname: Villarroel
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Guan
authors.forename: Evan
authors.initials: E
authors.lastname: Werlin
authors.forename: Ronald
authors.initials: R
authors.lastname: Figueredo
authors.forename: Lance B
authors.initials: LB
authors.lastname: Becker
authors.forename: Carrie
authors.initials: C
authors.lastname: Sims
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000473:pathology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D008929:Mitochondria, Heart / Q000502:physiology; D008930:Mitochondria, Liver / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000503:physiopathology / Q000628:therapy